Search

Congenital central hypoventilation syndrome (CCHS) is a rare condition characterized by central hypoventilation, leading to the majority of patients being dependent on ventilatory support during sleep. This condition is often accompanied by various associated symptoms, due to a PHOX2B gene variant involved in neuronal crest cell migration. This study is the first to review the characteristics and outcomes in children with CCHS on long-term mechanical ventilation in the Netherlands. We performed a retrospective study of all CCHS patients treated in the 4 Centers of Home Mechanical Ventilation of the University Medical Centers in the Netherlands from 2000 till 2022 by collecting information from the electronic medical records, documented during follow-up. We included 31 patients, out of which 27 exhibited a known genetic profile associated with CCHS, while no PHOX2B variant was identified in the remaining patients. Among the 27 patients with known genetic profiles, 10 patients had a non-polyalanine repeat expansion mutation (NPARM), followed by 20/27, 20/25, and 20/26 polyalanine repeat expansion mutations (PARMs) in descending order. The most common presentation involved respiratory failure or apneas during the neonatal period with an inability to wean off ventilation. The majority of patients required ventilatory support during sleep, with four patients experiencing life-threatening events related to this dependency. Daily use of ventilatory support varied among different genetic profiles. All genotypes reported comorbidities, with Hirschsprung's disease and cardiac arrhythmias being the most reported comorbidities. Notably, Hirschprung's disease was exclusively observed in patients with a 20/27 PHOX2B variant. Conclusion: Our study results suggest that in our cohort, the genotype is not easily associated to the phenotype in CCHS. Consistent with these findings and international literature, we recommend a thorough annual evaluation for all patients with CCHS to ensure optimal management and follow-up. What is Known: • The majority of CCHS patients are dependent on ventilatory support. • Variants in the PHOX2B gene are responsible for the characteristics of CCHS. What is New: • This study provides insight into the clinical course and long-term outcomes of CCHS patients in the Netherlands. • In CCHS, the genotype is not easily associated with the phenotype, requiring a thorough life-long follow-up for all patients. [ABSTRACT FROM AUTHOR]

Sudden cardiac arrest (SCA) studies are often population-based, limited to sudden cardiac death, and excluding infants. To guide prevention opportunities, it is essential to be informed of pediatric SCA etiologies. Unfortunately, etiologies frequently remain unresolved. The objectives of this study were to determine paediatric SCA etiology, and to evaluate the extent of post-SCA investigations and to assess the performance of previous cardiac evaluation in detecting conditions predisposing to SCA. In a retrospective cohort (2002–2019), all children 0–18 years with out-of-hospital cardiac arrest (OHCA) referred to Erasmus MC Sophia Children's Hospital or the Amsterdam UMC (tertiary-care university hospitals), with cardiac or unresolved etiologies were eligible for inclusion. SCA etiologies, cardiac and family history and etiologic investigations in unresolved cases were assessed. The etiology of arrest could be determined in 52% of 172 cases. Predominant etiologies in children ≥ 1 year (n = 99) were primary arrhythmogenic disorders (34%), cardiomyopathies (22%) and unresolved (32%). Events in children < 1 year (n = 73) were largely unresolved (70%) or caused by cardiomyopathy (8%), congenital heart anomaly (8%) or myocarditis (7%). Of 83 children with unresolved etiology a family history was performed in 51%, an autopsy in 51% and genetic testing in 15%. Pre-existing cardiac conditions presumably causative for SCA were diagnosed in 9%, and remained unrecognized despite prior evaluation in 13%. Conclusion: SCA etiology remained unresolved in 83 of 172 cases (48%) and essential diagnostic investigations were often not performed. Over one-fifth of SCA patients underwent prior cardiac evaluation, which did not lead to recognition of a cardiac condition predisposing to SCA in all of them. The diagnostic post-SCA approach should be improved and the proposed standardized pediatric post-SCA diagnostics protocol may ensure a consistent and systematic evaluation process increasing the diagnostic yield. What is Known: • Arrests in infants remain unresolved in most cases. In children > 1 year, predominant etiologies are primary arrhythmia disorders, cardiomyopathy and myocarditis. • Studies investigating sudden cardiac arrest are often limited to sudden cardiac death (SCD) in 1 to 40 year old persons, excluding infants and successfully resuscitated children. What is New: • In patients with unresolved SCA events, the diagnostic work up was often incompletely performed. • Over one fifth of victims had prior cardiac evaluation before the arrest, with either a diagnosed cardiac condition (9%) or an unrecognized cardiac condition (13%). [ABSTRACT FROM AUTHOR]

Calcific aortic stenosis is commonly treated using surgical or transcatheter aortic valve replacement; however, many patients are not considered suitable candidates for these interventions due to severe comorbidities and limited life expectancy. As such, non-invasive therapies might offer alternative therapeutic possibilities in these patients. This study aimed to assess the safety of non-invasive ultrasound therapy and its ability to improve valvular function by softening calcified valve tissue. This prospective, multicentre, single-arm series enrolled 40 adult patients with severe symptomatic aortic valve stenosis at three hospitals in France, the Netherlands, and Serbia between March 13, 2019, and May 8, 2022. Patients were treated with transthoracically delivered non-invasive ultrasound therapy. Follow-ups were scheduled at 1, 3, 6, 12, and 24 months. The primary endpoints were procedure-related deaths within 30 days and improved valve function. We report the 6-month data. This study is registered at ClinicalTrials.gov , NCT03779620 and NCT04665596. 40 high-risk patients with a mean Society of Thoracic Surgeons score of 5·6% (SD 4·4) and multiple severe comorbidities were included. The primary endpoint, procedure-related mortality, did not occur; furthermore, no life-threatening or cerebrovascular events were reported. Improved valve function was confirmed up to 6 months, reflected by a 10% increase in mean aortic valve area from 0·58 cm2 (SD 0·19) at baseline to 0·64 cm2 (0·21) at follow-up (p=0·0088), and a 7% decrease in mean pressure gradient from 41·9 mm Hg (20·1) to 38·8 mm Hg (17·8; p=0·024). At 6 months, the New York Heart Association score had improved or stabilised in 24 (96%) of 25 patients, and the mean Kansas City Cardiomyopathy Questionnaire score had improved by 33%, from 48·5 (SD 22·6) to 64·5 (21·0). One serious procedure-related adverse event occurred in a patient who presented with a transient decrease in peripheral oxygen saturation. Non-serious adverse events included pain, discomfort during treatment, and transient arrhythmias. This novel, non-invasive ultrasound therapy for calcified aortic stenosis proved to be safe and feasible. Cardiawave. [ABSTRACT FROM AUTHOR]

Background: People living with chronic obstructive pulmonary disease (COPD) have an increased risk of experiencing cardiovascular (CV) events, particularly after an exacerbation. Such CV burden is not yet known for incident COPD patients. We examined the risk of severe CV events in incident COPD patients in periods following either moderate and/or severe exacerbations. Methods: Persons aged ≥ 40 years with an incident COPD diagnosis from the PHARMO Data Network were included. Exposed time periods included 1–7, 8–14, 15–30, 31–180 and 181–365 days following an exacerbation. Moderate exacerbations were defined as those managed in outpatient settings; severe exacerbations as those requiring hospitalisation. The outcome was a composite of time to first severe CV event (acute coronary syndrome, heart failure decompensation, cerebral ischaemia, or arrhythmia) or death. Hazard ratios (HR) were estimated for association between each exposed period and outcome. Results: 8020 patients with newly diagnosed COPD were identified. 2234 patients (28%) had ≥ 1 exacerbation, 631 patients (8%) had a non-fatal CV event, and 461 patients (5%) died during a median follow-up of 36 months. The risk of experiencing the composite outcome was increased following a moderate/severe exacerbation as compared to time periods of stable disease [range of HR: from 15.3 (95% confidence interval 11.8–20.0) in days 1–7 to 1.3 (1.0–1.8) in days 181–365]. After a moderate exacerbation, the risk was increased over the first 180 days [HR 2.5 (1.3–4.8) in days 1–7 to 1.6 (1.3–2.1) in days 31–180]. After a severe exacerbation, the risk increased substantially and remained higher over the year following the exacerbation [HR 48.6 (36.9–64.0) in days 1–7 down to 1.6 (1.0–2.6) in days 181–365]. Increase in risk concerned all categories of severe CV events. Conclusions: Among incident COPD patients, we observed a substantial risk increase of severe CV events or all-cause death following either a moderate or severe exacerbation of COPD. Increase in risk was highest in the initial period following an exacerbation. These findings highlight the significant cardiopulmonary burden among people living with COPD even with a new diagnosis. [ABSTRACT FROM AUTHOR]

Aims Left ventricular (LV) blood flow is determined by intraventricular pressure gradients (IVPG). Changes in blood flow initiate remodelling and precede functional decline. Novel cardiac magnetic resonance (CMR) post-processing LV-IVPG analysis might provide a sensitive marker of LV function in dilated cardiomyopathy (DCM). Therefore, the aim of our study was to evaluate LV-IVPG patterns and their prognostic value in DCM. Methods and results LV-IVPGs between apex and base were measured on standard CMR cine images in DCM patients (n = 447) from the Maastricht Cardiomyopathy registry. Major adverse cardiovascular events, including heart failure hospitalisations, life-threatening arrhythmias, and sudden/cardiac death, occurred in 66 DCM patients (15%). A temporary LV-IVPG reversal during systolic–diastolic transition, leading to a prolonged transition period or slower filling, was present in 168 patients (38%). In 14%, this led to a reversal of blood flow, which predicted outcome corrected for univariable predictors [hazard ratio (HR) = 2.57, 95% confidence interval (1.01–6.51), P = 0.047]. In patients without pressure reversal (n = 279), impaired overall LV-IVPG [HR = 0.91 (0.83–0.99), P = 0.033], systolic ejection force [HR = 0.91 (0.86–0.96), P < 0.001], and E-wave decelerative force [HR = 0.83 (0.73–0.94), P = 0.003] predicted outcome, independent of known predictors (age, sex, New York Heart Association class ≥ 3, LV ejection fraction, late gadolinium enhancement, LV-longitudinal strain, left atrium (LA) volume-index, and LA-conduit strain). Conclusion Pressure reversal during systolic–diastolic transition was observed in one-third of DCM patients, and reversal of blood flow direction predicted worse outcome. In the absence of pressure reversal, lower systolic ejection force, E-wave decelerative force (end of passive LV filling), and overall LV-IVPG are powerful predictors of outcome, independent of clinical and imaging parameters. [ABSTRACT FROM AUTHOR]

RBM20 cardiomyopathy is an arrhythmogenic form of dilated cardiomyopathy caused by mutations in the splicing factor RBM20. A recent study found a more severe phenotype in male patients with RBM20 cardiomyopathy patients than in female patients. Here, we aim to determine sex differences in an animal model of RBM20 cardiomyopathy and investigate potential underlying mechanisms. In addition, we aim to determine sex and gender differences in clinical parameters in a novel RBM20 cardiomyopa)thy patient cohort. We characterized an Rbm20 knockout (KO) mouse model, and show that splicing of key RBM20 targets, car)diac function, and arrhythmia susceptibility do not differ between sexes. Next, we performed deep phenotyping of these mice, and show that male and female Rbm20-KO mice possess transcriptomic and phosphoproteomic differences. Hypothesizing that these differences may influence the heart’s ability to compensate for stress, we exposed Rbm20-KO mice to acute catecholami)nergic stimulation and again found no functional differences. We also replicate the lack of functional differences in a mouse model with the Rbm20-R636Q mutation. Lastly, we present a patient cohort of 33 RBM20 cardiomyopathy patients and show that these patients do not possess sex and gender differences in disease severity. Current mouse models of RBM20 cardiomy)opathy show more pronounced changes in gene expression and phosphorylation of cardiac proteins in male mice, but no sex differences in cardiac morphology and function. Moreover, other than reported before, male RBM20 cardiomyopathy patients do not present with worse cardiac function in a patient cohort from Germany and the Netherlands. NEW & NOTEWORTHY Optimal management of the cardiac disease is increasingly personalized, partly because of differences in outcomes between sexes. RBM20 cardiomyopathy has been described to be more severe in male patients, and this carries the risk that male patients are more scrutinized in the clinic than female patients. Our findings do not support this observation and suggest that treatment should not differ between male and female RBM20 cardiomyopathy patients, but instead should focus on the underlying disease mechanism. [ABSTRACT FROM AUTHOR]

Introduction: Patients with coronavirus disease 2019 (COVID-19) can present with chest pain. However, the characteristics of this chest pain are unknown. We performed a single-centre observational study to review and summarise chest pain characteristics in COVID-19 patients at first presentation to the emergency department (ED). Methods: We collected data on characteristics of 'chest pain' reported by COVID-19 patients who attended the ED of Bernhoven Hospital, the Netherlands from 4 through 30 March 2020. Results: We included 497 COVID-19 patients, of whom 83 (17%) reported chest pain upon presentation to the ED. Chest pain characteristics were: present since disease onset (88%), retrosternal location (43%), experienced as compressing/pressure pain (61%), no radiation (61%) and linked to heavy coughing (39%). Patients who reported chest pain were younger than those without chest pain (61 vs 73 years; p < 0.001). Patients with syncope were older (75 vs 72 years; p = 0.017), had a shorter duration of symptoms (5 vs 7 days; p < 0.001) and reported fewer respiratory complaints (68% vs 90%; p < 0.001) than those without syncope. Patients with new-onset atrial arrhythmias presented with a shorter duration of symptoms (5 vs 7 days; p = 0.013), experienced fewer respiratory complaints (72% vs 89%; p = 0.012) and more frequently had a history of cardiovascular disease (79% vs 50%; p = 0.003) than patients who presented without arrythmias. Conclusion: Chest pain and other cardiac symptoms were frequently observed in COVID-19 patients. Treating physicians should be aware that chest pain, arrhythmias and syncope can be presenting symptoms of COVID-19. [ABSTRACT FROM AUTHOR]

Background: Patients with cardiomyopathy of Duchenne Muscular Dystrophy (DMD) are at risk of developing life-threatening arrhythmias, but the mechanisms are unknown. We aimed to determine the role of ion channels controlling cardiac excitability in the mechanisms of arrhythmias in DMD patients. Methods: To test whether dystrophin mutations lead to defective cardiac NaV1.5-Kir2.1 channelosomes and arrhythmias, we generated iPSC-CMs from two hemizygous DMD males, a heterozygous female, and two unrelated control males. We conducted studies including confocal microscopy, protein expression analysis, patch-clamping, non-viral piggy-bac gene expression, optical mapping and contractility assays. Results: Two patients had abnormal ECGs with frequent runs of ventricular tachycardia. iPSC-CMs from all DMD patients showed abnormal action potential profiles, slowed conduction velocities, and reduced sodium (INa) and inward rectifier potassium (IK1) currents. Membrane NaV1.5 and Kir2.1 protein levels were reduced in hemizygous DMD iPSC-CMs but not in heterozygous iPSC-CMs. Remarkably, transfecting just one component of the dystrophin protein complex (a1-syntrophin) in hemizygous iPSC-CMs from one patient restored channelosome function, INa and IK1 densities, and action potential profile in single cells. In addition, a1-syntrophin expression restored impulse conduction and contractility and prevented reentrant arrhythmias in hiPSC-CM monolayers. Conclusions: We provide the first demonstration that iPSC-CMs reprogrammed from skin fibroblasts of DMD patients with cardiomyopathy have a dysfunction of the NaV1.5-Kir2.1 channelosome, with consequent reduction of cardiac excitability and conduction. Altogether, iPSC-CMs from patients with DMD cardiomyopathy have a NaV1.5-Kir2.1 channelosome dysfunction, which can be rescued by the scaffolding protein a1-syntrophin to restore excitability and prevent arrhythmias. Funding: Supported by National Institutes of Health R01 HL122352 grant; 'la Caixa' Banking Foundation (HR18-00304); Fundación La Marató TV3: Ayudas a la investigación en enfermedades raras 2020 (LA MARATO-2020); Instituto de Salud Carlos III/FEDER/FSE; Horizon 2020 - Research and Innovation Framework Programme GA-965286 to JJ; the CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia e Innovación (MCIN) and the Pro CNIC Foundation), and is a Severo Ochoa Center of Excellence (grant CEX2020-001041-S funded by MICIN/AEI/10.13039/501100011033). American Heart Association postdoctoral fellowship 19POST34380706s to JVEN. Israel Science Foundation to OB and MA [824/19]. Rappaport grant [01012020RI]; and Niedersachsen Foundation [ZN3452] to OB; US-Israel Binational Science Foundation (BSF) to OB and TH [2019039]; Dr. Bernard Lublin Donation to OB; and The Duchenne Parent Project Netherlands (DPPNL 2029771) to OB. National Institutes of Health R01 AR068428 to DM and US-Israel Binational Science Foundation Grant [2013032] to DM and OB. [ABSTRACT FROM AUTHOR]

Background and purpose: The electrocardiogram (ECG) is frequently obtained in the work-up of COVID-19 patients. So far, no study has evaluated whether ECG-based machine learning models have added value to predict in-hospital mortality specifically in COVID-19 patients. Methods: Using data from the CAPACITY-COVID registry, we studied 882 patients admitted with COVID-19 across seven hospitals in the Netherlands. Raw format 12-lead ECGs recorded within 72 h of admission were studied. With data from five hospitals (n = 634), three models were developed: (a) a logistic regression baseline model using age and sex, (b) a least absolute shrinkage and selection operator (LASSO) model using age, sex and human annotated ECG features, and (c) a pre-trained deep neural network (DNN) using age, sex and the raw ECG waveforms. Data from two hospitals (n = 248) was used for external validation. Results: Performances for models a, b and c were comparable with an area under the receiver operating curve of 0.73 (95% confidence interval [CI] 0.65–0.79), 0.76 (95% CI 0.68–0.82) and 0.77 (95% CI 0.70–0.83) respectively. Predictors of mortality in the LASSO model were age, low QRS voltage, ST depression, premature atrial complexes, sex, increased ventricular rate, and right bundle branch block. Conclusion: This study shows that the ECG-based prediction models could be helpful for the initial risk stratification of patients diagnosed with COVID-19, and that several ECG abnormalities are associated with in-hospital all-cause mortality of COVID-19 patients. Moreover, this proof-of-principle study shows that the use of pre-trained DNNs for ECG analysis does not underperform compared with time-consuming manual annotation of ECG features. [ABSTRACT FROM AUTHOR]

Aims: Drugs that prolong the QT interval, either by design (cardiac QT‐prolonging drugs: anti‐arrhythmics) or as off‐target effect (non‐cardiac QT‐prolonging drugs), may increase the risk of ventricular arrhythmias and out‐of‐hospital cardiac arrest (OHCA). Risk mitigation measures were instituted, in particular, surrounding prescription of cardiac QT‐prolonging drugs. We studied OHCA risk of both drug types in current clinical practice. Methods: Using data from large population‐based OHCA registries in the Netherlands and Denmark, we conducted two independent case–control studies. OHCA cases with presumed cardiac causes were matched on age/sex/index date with up to five non‐OHCA controls. We calculated odds ratios (ORs) for the association of cardiac or non‐cardiac QT‐prolonging drugs with OHCA risk using conditional logistic regression analyses. Results: We identified 2503 OHCA cases and 10 543 non‐OHCA controls in the Netherlands, and 35 017 OHCA cases and 175 085 non‐OHCA controls in Denmark. Compared to no use of QT‐prolonging drugs, use of non‐cardiac QT‐prolonging drugs (Netherlands: cases: 3.0%, controls: 1.9%; Denmark: cases: 14.9%, controls: 7.5%) was associated with increased OHCA risk (Netherlands: OR 1.37 [95% CI: 1.03–1.81]; Denmark: OR 1.63 [95% CI: 1.57–1.70]). The association between cardiac QT‐prolonging drugs (Netherlands: cases: 4.0%, controls: 2.5%; Denmark: cases: 2.1%, controls: 0.9%) and OHCA was weaker (Netherlands: OR 1.17 [95% CI: 0.92–1.50]; Denmark: OR 1.21 [95% CI: 1.09–1.33]), although users of cardiac QT‐prolonging drugs had more medication use and comorbidities associated with OHCA risk than users of non‐cardiac QT‐prolonging drugs. Conclusion: In clinical practice, cardiac QT‐prolonging drugs confer lower OHCA risk than non‐cardiac QT‐prolonging drugs, although users of the former have higher a priori risk. This is likely due to risk mitigation measures surrounding prescription of cardiac QT‐prolonging drugs. [ABSTRACT FROM AUTHOR]

Purpose: Integrated care models have shown to deliver efficient healthcare, but implementation has proven to be difficult. The Support Consultation is an integrated care model, which enables full integration by bundled payment, insurer involvement, predefined care pathways and strengthening of primary care. The purpose of this paper is to provide an indication of the improvements in healthcare delivery after implementation of this proposed model and to create a base for extension to similar interfaces between primary and secondary care. Design/methodology/approach: A retrospective study was used to compare the effect on the number of referred patients with non-acute cardiac complaints and the cost effectiveness before and after implementation of the Support Consultation. Patients who previously would have been referred to the cardiologist were now discussed between general practitioner and cardiologist in a primary care setting. Findings: The first consecutive 100 patients (age 55±16 years, male 48 percent), discussed in the Support Consultation, were analyzed. Implementation of the Support Consultation resulted in a net costs (program costs and referral costs) reduction of 61 percent compared with usual care. All involved parties were positive about the program. Research limitations/implications: The Support Consultation has the ability to provide more effective healthcare delivery and to reduce net costs. The setting of the current study can be used as example for other specialties in countries with a similar healthcare system. Originality/value: This study provides the potential cost savings after implementation of an integrated care model, based on real-life data. [ABSTRACT FROM AUTHOR]

Background Numerous drugs prolong the QTc interval on the ECG and potentially increase the risk of cardiac arrhythmia. This risk is clinically relevant in patients with additional risk factors. Objective The objective was to develop and validate a risk model to predict QTc interval prolongation of eligible ECGs. Setting Spaarne Gasthuis (Haarlem/Hoofddorp, The Netherlands). Method A dataset was created from ECGs recorded in patients using one or more QTc prolonging drugs, in the period January 2013 and October 2016. In the development set, independent risk factors for QTc interval prolongation were determined using binary logistic regression. Risk scores were assigned based on the beta coefficient. In the risk-score validation set, the area under the ROC-curve, sensitivity and specificity were calculated. Main outcome measure QTc interval prolongation, defined as a QTc interval > 500 ms. Results In the development set 12,949 ECGs were included and in the risk-score validation set 6391 ECGs. The proportion of ECGs with a prolonged QTc interval in patients with no risk factors in the risk-score validation set was 2.7%, while in patients with a high risk score the proportion was 26.1%. The area under the ROC curve was 0.71 (95% CI 0.68-0.73). The sensitivity and specificity were 0.81 and 0.48, respectively. Conclusion A risk model was developed and validated for the prediction of QTc interval prolongation. This risk model can be implemented in a clinical decision support system, supporting the management of the risks involved with QTc interval prolonging drugs. [ABSTRACT FROM AUTHOR]

This section highlights the results of selected health research as of November 1, 2022. Exposure to small-particle air pollution has been linked to increased risk of irregular heartbeats in otherwise healthy adolescents in the U.S. Family caregivers were marginalised and vulnerable older people were let down by the health system in Great Britain during the COVID-19 pandemic. Health communication does not reduce chlamydia and gonorrhoea reinfection rates in young people in Great Britain.

Purpose: After regulatory restrictions for terfenadine and astemizole in '90s, only scarce evidence on proarrhythmic potential of antihistamines has been published. We evaluate the risk of ventricular tachyarrhythmia (VA) related to the use of individual antihistamines. Methods: A matched case-control study nested in a cohort of new users of antihistamines was conducted within the EU-funded ARITMO project. Data on 1997-2010 were retrieved from seven healthcare databases: AARHUS (Denmark), GEPARD (Germany), HSD and ERD (Italy), PHARMO and IPCI (Netherlands) and THIN (UK). Cases of VA were selected and up to 100 controls were matched to each case. The odds ratio (OR) of current use for individual antihistamines (AHs) was estimated using conditional logistic regression. Results: For agents largely used to prevent allergic symptoms, such as cetirizine, levocetirizine, loratadine, desloratadine and fexofenadine, we found no VA risk. A statistically significant, increased risk of VA was found only for current use of cyclizine in the pooled analysis (ORadj, 5.3; 3.6-7.6) and in THIN (ORadj, 5.3; 95% CI, 3.7-7.6), for dimetindene in GEPARD (ORadj, 3.9; 1.1-14.7) and for ebastine in GEPARD (ORadj, 3.3; 1.1-10.8) and PHARMO (ORadj, 4.6; 1.3-16.2). Conclusions: The risk of VA associated with a few specific antihistamines could be ascribable to heterogeneity in pattern of use or in receptor binding profile. [ABSTRACT FROM AUTHOR]

Introduction: Vomiting in the emergency department after trauma occurs frequently and might lead to aspiration of gastric content. An orogastric tube (OGT) is a way to prevent emesis. However, this is an inconvenient procedure and may actually trigger vomiting. Therefore, a change in policy was applied from preferably an OGT to the administration of anti-emetics in a selected population. The aim of this study was to analyse the prevention of vomiting in trauma patients after OGT or anti-emetics.Materials and Methods: Retrospective cohort study. Data of all trauma patients presented at the crash room of the emergency department between July 1st 2013 and July 1st 2014 were collected from the local trauma registry and electronic patient documentation system and comprising 6 months preceding and 6 months after change of policy. Vomiting and nausea after trauma were recorded. Furthermore, complications such as aspiration and cardiac arrhythmias were documented.Results: A total of 1446 patients were presented after trauma. 230 patients were promptly intubated. An additional 763 patients were fully responsive and did not complain of nausea. The remaining 453 patients were further analysed. 44 patients received OGT placement procedure and 409 patients received anti-emetics. Significant difference was found in patients vomiting after OGT placement or anti-emetics (20.5% vs. 2.7%; P<0.001). Patients who received anti-emetics were not more at risk for cardiac arrhythmias. After matched control analysis, there was still a significant difference was found.Discussion and Conclusion: Administration of anti-emetics is suitable and effective for the prevention of vomiting after trauma in this selected population, without an increased risk for complications. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to evaluate the incidence of complications in elderly patients with a hip fracture following integrated orthogeriatric treatment. To discover factors that might be adjusted, in order to improve outcome in those patients, we examined the association between baseline patient characteristics and a complicated course.Methods: We included patients aged 70 years and older with a hip fracture, who were treated at the Centre for Geriatric Traumatology (CvGT) at Ziekenhuisgroep Twente (ZGT) Almelo, the Netherlands between April 2011 and October 2013. Data registration was carried out using the clinical pathways of the CvGT database. Based on the American Society of Anesthesiologists (ASA) score, patients were divided into high-risk (HR, ASA 3 ≥, n = 341) and low-risk (LR, ASA 1-2, n = 111) groups and compared on their recovery. Multivariate logistic regression was used to identify risk factors for a complicated course.Results: The analysis demonstrated that 49.6% (n = 224) of the patients experienced a complicated course with an in-hospital mortality rate of 3.8% (n = 17). In 57.5% (n = 196) of the HR patients, a complicated course was seen compared to 25.2% (n = 28) of the LR patients. The most common complications in both groups were the occurrence of delirium (HR 25.8% vs. LR 8.1%, p ≤ 0.001), anemia (HR 19.4% vs. LR 6.3%, p = 0.001), catheter-associated urinary tract infections (CAUTIs) (HR 10.6% vs. LR 7.2%, p = 0.301) and pneumonia (HR 10.9% vs. LR 5.4%, p = 0.089). Independent risk factors for a complicated course were increasing age (OR 1.04, 95% CI 1.01-1.07, p = 0.023), delirium risk VMS Frailty score (OR 1.57, 95% CI 1.04-2.37, p = 0.031) and ASA score ≥3 (OR 3.62, 95% CI 2.22-5.91, p ≤ 0.001).Conclusions: After integrated orthogeriatric treatment, a complicated course was seen in 49.6% of the patients with a hip fracture. The in-hospital mortality rate was 3.8%. Important risk factors for a complicated course were increasing age, poor medical condition and delirium risk VMS Frailty score. Awareness of risk factors that affect the course during admission can be useful in optimizing care and outcomes. In the search for possible areas for improvement in care, targeted preventive measures to mitigate delirium, and healthcare-associated infections (HAIs), such as CAUTIs and pneumonia are important. [ABSTRACT FROM AUTHOR]

Objective: To provide prospective information on long-term outcome after surgical correction of valvular pulmonary stenosis (PS).Methods: Fifty-three consecutive patients operated for PS during childhood between 1968 and 1980 in one centre are followed longitudinally for 37±3.4 years, including extensive in-hospital examination every 10 years.Results: Survival information was available in 100% of the original 53 patients. Cumulative survival was 94% at 20 years and 91% at 40 years. Excluding perioperative mortality (<30 days), survival was 94% at 40 years. Of 46 eligible survivors, 29 participated in the in-hospital examination and 15 gave permission to use their hospital records (96% participation). Cumulative event-free survival was 68% after 40 years: 25% needed a reintervention, 12% underwent pacemaker implantation and 9% had supraventricular arrhythmias. Early reinterventions were mainly for residual PS, late reinterventions for pulmonary regurgitation. Subjective health status was good. Exercise capacity was normal in 74% (median 96 (82-107)% of expected workload). Right ventricular and left ventricular (LV) dysfunction was found in 13% and 41%, respectively. The use of a transannular patch and younger age at surgery were predictive for late events (HR 3.02 (95% CI 1.09 to 8.37) and HR 0.81/year (95% CI 0.66 to 0.98), respectively). Use of inflow occlusion compared with cardiopulmonary bypass showed a trend towards more reinterventions (HR 3.19 (95% CI 0.97 to 10.47)).Conclusions: Survival up to 40 years after successful PS repair is nearly normal. Subjective health status is good and there is a low incidence of arrhythmias. Reinterventions, however, are necessary in one-quarter and 40 years postoperatively several patients show LV dysfunction. [ABSTRACT FROM AUTHOR]

Background: Mutations in LMNA are variably expressed and may cause cardiomyopathy, atrioventricular block (AVB), or atrial arrhythmias (AAs) and ventricular arrhythmias (VA). Detailed natural history studies of LMNA-associated arrhythmic and nonarrhythmic outcomes are limited, and the prognostic significance of the index cardiac phenotype remains uncertain.Objectives: This study sought to describe the arrhythmic and nonarrhythmic outcomes of LMNA mutation carriers and to assess the prognostic significance of the index cardiac phenotype.Methods: The incidence of AVB, AA, sustained VA, left ventricular systolic dysfunction (LVD) (= left ventricular ejection fraction ≤50%), and end-stage heart failure (HF) was retrospectively determined in 122 consecutive LMNA mutation carriers followed at 5 referral centers for a median of 7 years from first clinical contact. Predictors of VA and end-stage HF or death were determined.Results: The prevalence of clinical manifestations increased broadly from index evaluation to median follow-up: AVB, 46% to 57%; AA, 39% to 63%; VA, 16% to 34%; and LVD, 44% to 57%. Implantable cardioverter-defibrillators were placed in 59% of patients for new LVD or AVB. End-stage HF developed in 19% of patients, and 13% died. In patients without LVD at presentation, 24% developed new LVD, and 7% developed end-stage HF. Male sex (p = 0.01), nonmissense mutations (p = 0.03), and LVD at index evaluation (p = 0.004) were associated with development of VA, whereas LVD was associated with end-stage HF or death (p < 0.001). Mode of presentation (with isolated or combination of clinical features) did not predict sustained VA or end-stage HF or death.Conclusions: LMNA-related heart disease was associated with a high incidence of phenotypic progression and adverse arrhythmic and nonarrhythmic events over long-term follow-up. The index cardiac phenotype did not predict adverse events. Genetic diagnosis and subsequent follow-up, including anticipatory planning for therapies to prevent sudden death and manage HF, is warranted. [ABSTRACT FROM AUTHOR]

Background: Risk prediction of atrial fibrillation (AF) is of importance to improve the early diagnosis and treatment of AF. Latent class analysis takes into account the possible existence of classes of individuals each with shared risk factors, and maybe a better method of incorporating the phenotypic heterogeneity underlying AF. Methods and findings: Two prospective community-based cohort studies from Netherlands and United States were used. Prevention of Renal and Vascular End-stage Disease (PREVEND) study, started in 1997, and the Framingham Heart Study (FHS) Offspring cohort started in 1971, both with 10-years follow-up. The main objective was to determine the risk of AF using a latent class analysis, and compare the discrimination and reclassification performance with traditional regression analysis. Mean age in PREVEND was 49±13 years, 49.8% were men. During follow-up, 250(3%) individuals developed AF. We built a latent class model based on 18 risk factors. A model with 7 distinct classes (ranging from 341 to 1517 individuals) gave the optimum tradeoff between a high statistical model-likelihood and a low number of model parameters. All classes had a specific profile. The incidence of AF varied; class 1 0.0%, class 2 0.3%, class 3 7.5%, class 4 0.2%, class 5 1.3%, class 6 4.2%, class 7 21.7% (p<0.001). The discrimination (C-statistic 0.830 vs. 0.842, delta-C -0.013, p = 0.22) and reclassification (IDI -0.028, p<0.001, NRI -0.090, p = 0.049, and category-less-NRI -0.049, p = 0.495) performance of both models was comparable. The results were successfully replicated in a sample of the FHS study (n = 3162; mean age 58±9 years, 46.3% men). Conclusions: Latent class analysis to build an AF risk model is feasible. Despite the heterogeneity in number and severity of risk factors between individuals at risk for AF, latent class analysis produces distinguishable groups. [ABSTRACT FROM AUTHOR]

Background: The impact of intravenous (IV) beta-blockers before primary percutaneous coronary intervention (PPCI) on infarct size and clinical outcomes is not well established.Objectives: This study sought to conduct the first double-blind, placebo-controlled international multicenter study testing the effect of early IV beta-blockers before PPCI in a general ST-segment elevation myocardial infarction (STEMI) population.Methods: STEMI patients presenting <12 h from symptom onset in Killip class I to II without atrioventricular block were randomized 1:1 to IV metoprolol (2 × 5-mg bolus) or matched placebo before PPCI. Primary endpoint was myocardial infarct size as assessed by cardiac magnetic resonance imaging (CMR) at 30 days. Secondary endpoints were enzymatic infarct size and incidence of ventricular arrhythmias. Safety endpoints included symptomatic bradycardia, symptomatic hypotension, and cardiogenic shock.Results: A total of 683 patients (mean age 62 ± 12 years; 75% male) were randomized to metoprolol (n = 336) or placebo (n = 346). CMR was performed in 342 patients (54.8%). Infarct size (percent of left ventricle [LV]) by CMR did not differ between the metoprolol (15.3 ± 11.0%) and placebo groups (14.9 ± 11.5%; p = 0.616). Peak and area under the creatine kinase curve did not differ between both groups. LV ejection fraction by CMR was 51.0 ± 10.9% in the metoprolol group and 51.6 ± 10.8% in the placebo group (p = 0.68). The incidence of malignant arrhythmias was 3.6% in the metoprolol group versus 6.9% in placebo (p = 0.050). The incidence of adverse events was not different between groups.Conclusions: In a nonrestricted STEMI population, early intravenous metoprolol before PPCI was not associated with a reduction in infarct size. Metoprolol reduced the incidence of malignant arrhythmias in the acute phase and was not associated with an increase in adverse events. (Early-Beta blocker Administration before reperfusion primary PCI in patients with ST-elevation Myocardial Infarction [EARLY-BAMI]; EudraCT no: 2010-023394-19). [ABSTRACT FROM AUTHOR]

Aims: Implantable cardiac monitors (ICMs) are used for long-term heart rhythm monitoring, e.g. to diagnose unexplained syncope or for detection of suspected atrial and ventricular arrhythmias. The newest ICM, Reveal LINQ™ (Medtronic Inc.), is miniaturized and inserted with a specific insertion tool kit. The procedure is therefore minimally invasive and can be moved from catheterization laboratory (cath lab) to a less resource intensive setting. This study aims to assess the change in procedure costs when performed outside the cath lab.Methods and Results: A bottom-up costing methodology was used. Data were collected from interviews with physicians, cath lab managers, and financial controllers. Hospitals in the Netherlands, France, and the UK were included in this study. The cost comparison of a Reveal XT implantation in a cath lab setting vs. a Reveal LINQ insertion outside a cath lab resulted in an estimated reduction of €662 for the UK, €682 for the Netherlands, and €781 for France. These cost savings were primarily realized through fewer staff, less equipment, and overhead costs. The net effect on savings depends on the price differential between these two technologies. The patient care pathway can be improved due to the possibility to move the procedure out of the cath lab.Conclusion: Inserting the miniaturized version of the ICM is simpler and faster, and the procedure can take place outside the cath lab in a less resource intensive environment. Hospitals save resources when the higher price of the Reveal LINQ does not outweigh these savings. [ABSTRACT FROM AUTHOR]

Background: Stroke prevention is the main goal of treating patients with atrial fibrillation (AF). Vitamin-K antagonists (VKAs) present an effective treatment in stroke prevention, however, the risk of bleeding and the requirement for regular coagulation monitoring are limiting their use. Apixaban is a novel oral anticoagulant associated with significantly lower hazard rates for stroke, major bleedings and treatment discontinuations, compared to VKAs. Objective: To estimate the cost-effectiveness of apixaban compared to VKAs in non-valvular AF patients in the Netherlands. Methods: Previously published lifetime Markov model using efficacy data from the ARISTOTLE and the AVERROES trial was modified to reflect the use of oral anticoagulants in the Netherlands. Dutch specific costs, baseline population stroke risk and coagulation monitoring levels were incorporated. Univariate, probabilistic sensitivity and scenario analyses on the impact of different coagulation monitoring levels were performed on the incremental cost-effectiveness ratio (ICER). Results: Treatment with apixaban compared to VKAs resulted in an ICER of €10,576 per quality adjusted life year (QALY). Those findings correspond with lower number of strokes and bleedings associated with the use of apixaban compared to VKAs. Univariate sensitivity analyses revealed model sensitivity to the absolute stroke risk with apixaban and treatment discontinuations risks with apixaban and VKAs. The probability that apixaban is cost-effective at a willingness-to-pay threshold of €20,000/QALY was 68%. Results of the scenario analyses on the impact of different coagulation monitoring levels were quite robust. Conclusions: In patients with non-valvular AF, apixaban is likely to be a cost-effective alternative to VKAs in the Netherlands. [ABSTRACT FROM AUTHOR]

Background: Exercise is associated with sustained ventricular arrhythmias (VA) in Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) but is not included in the ARVC risk calculator (arvcrisk.com). The objective of this study is to quantify the influence of exercise at diagnosis on incident VA risk and evaluate whether the risk calculator needs adjustment for exercise.Methods: We interviewed ARVC patients without sustained VA at diagnosis about their exercise history. The relationship between exercise dose 3 years preceding diagnosis (average METh/wk) and incident VA during follow-up was analyzed with time-to-event analysis. The incremental prognostic value of exercise to the risk calculator was evaluated by Cox models.Results: We included 176 patients (male, 43.2%; age, 37.6±16.1 years) from 3 ARVC centers, of whom 53 (30.1%) developed sustained VA during 5.4 (2.7-9.7) years of follow-up. Exercise at diagnosis showed a dose-dependent nonlinear relationship with VA, with no significant risk increase <15 to 30 METh/wk. Athlete status, using 3 definitions from literature (>18, >24, and >36 METh/wk), was significantly associated with VA (hazard ratios, 2.53-2.91) but was also correlated with risk factors currently in the risk calculator model. Thus, adding athlete status to the model did not change the C index of 0.77 (0.71-0.84) and showed no significant improvement (Akaike information criterion change, <2).Conclusions: Exercise at diagnosis was dose dependently associated with risk of sustained VA in ARVC patients but only above 15 to 30 METh/wk. Exercise does not appear to have incremental prognostic value over the risk calculator. The ARVC risk calculator can be used accurately in athletic patients without modification. [ABSTRACT FROM AUTHOR]

The primary goal of this observational clinical study was to register the occurrence of incorrect inflation and deflation timing of an intra-aortic balloon pump in autoPilot mode. The secondary goal was to identify possible causes of incorrect timing. During IABP assistance of 60 patients, every four hours a strip was printed with the IABP frequency set to 1:2. Strips were examined for timing discrepancies beyond 40 ms from the dicrotic notch (inflation) and the end of the diastolic phase (deflation). In this way, 320 printed strips were examined. A total of 52 strips (16%) showed incorrect timing. On 24 of these strips, the incorrect timing was called incidental, as it showed on only one or a few beats. The other 28 cases of erroneous timing were called consistent, as more than 50% of the beats on the strip showed incorrect timing. We observed arrhythmia in 69% of all cases of incorrect timing. When timing was correct, arrhythmia was found on 13 (5%) of 268 strips. A poor quality electrocardiograph (ECG) signal showed on 37% of all strips with incorrect timing and 11% of all strips with proper timing. We conclude that inflation and deflation timing of the IABP is not always correct when using the autoPilot mode. The quality of the ECG input signal and the occurrence of arrhythmia appear to be related to erroneous timing. Switching from autoPilot mode to operator mode may not always prevent incorrect timing. [ABSTRACT FROM AUTHOR]

Background-Over the last decades, a gradual decrease in ventricular fibrillation (VF) as initial recorded rhythm during resuscitation for out-of-hospital cardiac arrest (OHCA) has been noted. We sought to establish the contribution of implantable cardioverter-defibrillator (ICD) therapy to this decline. Methods and Results-Using a prospective database of all OHCA resuscitation in the province North Holland in the Netherlands (Amsterdam Resuscitation Studies [ARREST]), we collected data on all patients in whom resuscitation for OHCA was attempted in 2005-2008. VF OHCA incidence (per 100 000 inhabitants per year) was compared with VF OHCA incidence data during 1995-1997, collected in a similar way. We also collected ICD interrogations of all ICD patients from North Holland and identified all appropriate ICD shocks in 2005-2008; we calculated the number of prevented VF OHCA episodes, considering that only part of the appropriate shocks would result in avoided resuscitation. VF OHCA incidence decreased from 21.1/100 000 in 1995-1997 to 17.4/100 000 in 2005-2008 (P<0.00l). Non-VF OHCA increased from 12.2/100 000 to 19.4/100 000 (P<0.001). VF as presenting rhythm declined from 63% to 47%. In 2005-2008, 1972 ICD patients received 977 shocks. Of these shocks, 339 were caused by a life-threatening arrhythmia. We estimate that these 339 shocks have prevented 81 (minimum, 39; maximum, 152) cases of VF OHCA, corresponding with 33% (minimum, 16%; maximum, 63%) of the observed decline in VF OHCA incidence. - Conclusions-The incidence of VF OHCA decreased over the last 10 years in North Holland. ICD therapy explained a decrease of 1.2/100 000 inhabitants per year, corresponding with 33% of the observed decline in VP OHCA. [ABSTRACT FROM AUTHOR]

Objective Systemic sclerosis (SSc) is a connective tissue disease characterized by vascular inflammation and fibrosis. Visceral involvement, including cardiac manifestations, can lead to severe clinical complications, such as congestive heart failure, arrhythmias, and sudden death. Conventional echocardiography parameters have limited sensitivity to detect subtle myocardial dysfunction in patients with SSc. The aim of this study was to assess, using novel speckle-tracking strain analysis, the presence of myocardial dysfunction in patients with SSc, and to investigate its relationship to functional capacity and ventricular arrhythmias. Methods A total of 104 patients with SSc (mean ± SD age 54 ± 12 years, 77% female) were included and underwent cardiopulmonary exercise testing, 24-hour electrocardiography (EKG) Holter monitoring, and transthoracic echocardiography. For comparison, 37 matched healthy control subjects were included. Results The total patient population consisted of 51 patients with limited cutaneous SSc and 53 with diffuse cutaneous SSc. Peak V O2 was a mean ± SD 91 ± 20% predicted, and 28 patients had abnormal findings (ventricular tachycardia or ventricular ectopics >100/day) on EKG Holter monitoring. Patients with SSc, as compared with controls, had impaired global longitudinal and circumferential strains (mean ± SD −18.2 ± 1.8% versus −21.3 ± 1.7% and −18.2 ± 2.3% versus −21.3 ± 2.1%, respectively; each P < 0.01), but there was no difference in the left ventricular ejection fraction between patients and controls (mean ± SD 63.5 ± 7.2% versus 64.6 ± 4.4%; P = 0.20). In patients with SSc, global longitudinal and circumferential strains each correlated with the peak V O2 (r = −0.46 and r = −0.41, respectively; both P < 0.01), and multivariate analysis confirmed the independent association of each strain measure with the peak V O2. Compared to SSc patients with normal results on EKG Holter monitoring, SSc patients with abnormal results showed impaired global longitudinal strains (−18.5 ± 1.5% versus −17.1 ± 2.1%; P < 0.01) and circumferential strains (−18.7 ± 2.0% versus −17.3 ± 2.5%; P = 0.01), and each strain measure was independently associated with abnormal Holter findings. Conclusion Speckle-tracking strain analysis can detect subtle myocardial dysfunction in patients with SSc. Importantly, decreased global longitudinal and circumferential strains are associated with lower functional capacity and rhythm disturbances in patients with SSc. [ABSTRACT FROM AUTHOR]

Abstract: Background: Heavy alcohol use as well as alcohol dependence (AD) have been associated with dysregulation of the hypothalamic–pituitary–adrenal (HPA)-axis and the autonomic nervous system (ANS). However, the relative contribution of alcohol use and AD is unclear. Methods: Baseline data were derived from 2947 persons of the Netherlands Study of Depression and Anxiety (NESDA), including non-drinkers (n =498), moderate drinkers (n =2112) and heavy drinkers (n =337). We also distinguished between persons with no lifetime DSM-IV AD (n =2496), remitted AD (>1 year; n =243), and current AD (≤1 year; n =208). ANS measures included ECG-based heart rate (HR), respiratory sinus arrhythmia (RSA, high RSA reflecting high cardiac parasympathetic control) and pre-ejection period (PEP, high PEP reflecting low cardiac sympathetic control). HPA-axis measures included the cortisol awakening response (area under the curve with respect to the ground [AUCg] and increase [AUCi]), evening cortisol and a 0.5mg dexamethasone suppression test, all measured in saliva. Results: Heavy drinkers showed higher basal cortisol levels (AUCg: p =.02; evening cortisol: p =.006) and increased cardiac sympathetic control (higher HR: p =.04; lower PEP: p =.04) compared to moderate drinkers. Persons with current or remitted AD did not differ from persons without lifetime AD on any of the HPA-axis or ANS indicators (all p >.33). Similar patterns of HPA-axis and ANS activity across alcohol use groups were found in persons with and without lifetime AD. Conclusions: Our findings suggest that current heavy alcohol use, rather than current or remitted AD, is associated with hyperactivity of the HPA-axis and increased cardiac sympathetic control. [Copyright &y& Elsevier]

Objective To assess the extent and the characteristics of hospital admissions in registered adult patients with congenital heart disease. Design Observational cohort study. Setting The Netherlands. Patients 5798 adult patients with congenital heart disease from the Dutch CONCOR national registry linked to the Dutch National Medical Registration (Prismant). Main outcome measures All hospital admissions from the years 2001 up until 2006. Results During 28⇔990 patient-years, 2908 patients (50%) were admitted to hospital. Median age at admission was 39 years (range 18-86 years); 46% were male. Admission rate in CONCOR patients was high among all ages (range 11-68%) and exceeded that of the general Dutch population two to three times; this difference was most pronounced in the older age groups. Altogether there were 8916 admissions, 5411 (61%) of which were for cardiovascular indications. Among cardiovascular admissions, referrals for arrhythmias were most common (31%). Of 4926 interventions, 2459 (50%) were cardiovascular, most often reparative interventions or cardioversion (53%). Most non-cardiovascular admissions were obstetric. Among defects, univentricular heart and tricuspid atresia had the highest incidence and duration of admission. Conclusions Healthcare utilisation in registered and medically supervised adult patients with congenital heart disease is high and increases with age. Admission rates are at least two times higher than in the general population, and most marked in the older age groups. With the ageing of this population, a major increase in healthcare utilisation is imminent in the near future. Timely preparation of healthcare resources is crucial to sustain optimal care. [ABSTRACT FROM AUTHOR]

AbstractObjective:To determine in the Netherlands what proportions of high risk patients with established cardiovascular disease (CVD) or diabetes mellitus type 2 (DM2) who were not treated with statins on 1 January 2007 and which characteristics were associated with non-treatment.Methods:From the IPCI GP database patients were selected who were registered with a GP on 1 January 2007 who had a history of either CVD (CVD patients), DM2 (diabetics) or both (diabetics with CVD). The proportion of patients using statins around 1 January 2007 was determined. Associations of patient characteristics with non-treatment were quantified (CVD patients and diabetics only).Results:In all, 19 628 CVD patients, 5006 diabetics and 3767 diabetics with CVD were identified. Of these patients 71, 54 and 45, respectively did not use statins. These proportions were similar in the subgroups of patients with recent LDL-C measurements. Among these subgroups the vast majority of non-treated patients was eligible for statin treatment (LDL-C >2.5 mmol/l). The proportion of statin-treated patients was larger among diabetics than among CVD patients. Among CVD patients, female gender, age below 40 years, living in a deprived area, a history of CVD of less than 1 year and arrhythmia were significantly associated with non-treatment. Among diabetics, significant associations were: living in a deprived area and specialist visits in the previous year. In 2003, treatment rates among diabetics were lower, but among CVD patients they were similar. This suggests that the higher treatment rates among diabetics compared to CVD patients in 2007 may be the result of disease-management programmes introduced for diabetics in 2004.Conclusion:The majority of patients with established CVD or DM2 were not treated with statins on 1 January 2007. Eligibility for statin treatment may have been overestimated due to unavailability of cholesterol levels among many non-treated patients. Implementation of care programmes for CVD patients may increase treatment rates among eligible CVD patients. [ABSTRACT FROM AUTHOR]

The article discusses the association between major depressive disorder and heart rate variability in the Netherlands Study of Depression and Anxiety (NESDA). It examines whether heart rate variability was lower in depressed individuals than in healthy controls. It was found that individuals with remitted and current major depressive disorder had a lower mean standard deviation of normal-to-normal beats (SDNN) and respiratory sinus arrhythmia (RSA) compared with healthy controls. The author concludes that depression is associated with significantly lowered heart rate variability, which is mainly driven by the effect of antidepressants.

Background: Cardiac resynchronization therapy (CRT) is an established therapy in patients with dilated cardiomyopathy (DCM) and conduction disorders. Still, one-third of the patients with DCM do not respond to CRT. This study aims to depict the underlying cardiac pathophysiological processes of nonresponse to CRT in patients with DCM using endomyocardial biopsies.Methods: Within the Maastricht and Innsbruck registries of patients with DCM, 99 patients underwent endomyocardial biopsies before CRT implantation, with histological quantification of fibrosis and inflammation, where inflammation was defined as >14 infiltrating cells/mm2. Echocardiographic left ventricular end-systolic volume reduction ≥15% after 6 months was defined as response to CRT. RNA was isolated from cardiac biopsies of a representative subset of responders and nonresponders.Results: Sixty-seven patients responded (68%), whereas 32 (32%) did not respond to CRT. Cardiac inflammation before implantation was negatively associated with response to CRT (25% of responders, 47% of nonresponders; odds ratio 0.3 [0.12-0.76]; P=0.01). Endomyocardial biopsies fibrosis did not relate to CRT response. Cardiac inflammation improved the robustness of prediction beyond well-known clinical predictors of CRT response (likelihood ratio test P<0.001). Cardiac transcriptomic profiling of endomyocardial biopsies reveals a strong proinflammatory and profibrotic signature in the hearts of nonresponders compared with responders. In particular, COL1A1, COL1A2, COL3A1, COL5A1, POSTN, CTGF, LOX, TGFβ1, PDGFRA, TNC, BGN, and TSP2 were significantly higher expressed in the hearts of nonresponders.Conclusions: Cardiac inflammation along with a transcriptomic profile of high expression of combined proinflammatory and profibrotic genes are associated with a poor response to CRT in patients with DCM. [ABSTRACT FROM AUTHOR]

Background: Right ventricular (RV) pacing in implantable cardioverter-defibrillator (ICD) patients may have detrimental effects on morbidity and mortality, in particular by inducing heart failure (HF). Objective: We investigated whether RV pacing increases the risk of HF in an asymptomatic ICD population. Methods: We evaluated all patients without symptomatic HF who received an ICD. The primary endpoint was the occurrence of HF, which was defined as new HF, hospitalization for HF, or death due to HF. The secondary endpoint was appropriate shocks. Results: The study population consisted of 456 patients with mean left ventricular ejection fraction (LVEF) 40% ± 13%. Mean follow-up was 31 ± 22 months. Because of the bimodal distribution of pacing, patients were divided into two groups: paced ≤50% (median 0%; n = 313) and paced >50% (median 96%; n = 143). HF occurred more often in the paced >50% group (20% versus 9%; P <.001). Multivariate analysis identified RV pacing >50% (adjusted hazard ratio [HR] 1.85; 95% confidence interval [CI] 1.08–3.15; P = .03), baseline LVEF <26% (adjusted HR 3.15; 95% CI 1.77–5.59; P <.001), angina pectoris, history of atrial fibrillation, and baseline diuretic use as independent predictors of HF. RV pacing caused more HF events in patients with LVEF <26% (n = 64; 55% of paced >50% patients versus 20% of paced ≤50% patients; P = .006). RV pacing >50% also independently predicted appropriate shocks (adjusted HR 1.50; 95% CI 1.02–2.20; P = .04). Conclusion: RV pacing was associated with an increased risk of HF in asymptomatic ICD patients, particularly in those with preexistent left ventricular dysfunction. [Copyright &y& Elsevier]

Introduction: Lidocaine is an effective drug for the treatment of neonatal convulsions not responding to traditional anticonvulsant therapy. However, one of the side-effects is a risk of cardiac arrhythmias. The aim of this study was to develop an optimal dosing strategy with minimal risk of cardiac arrhythmias.Materials and Methods: As a first step, we studied 20 neonates during routine treatment of neonatal seizures with lidocaine. All were given a loading dose of 2 mg/kg in 10 min, followed by the continuous infusion of 6 mg/kg per hour for 12 h, 4 mg/kg per hour for 12 h and finally 2 mg/kg per hour for 12 h. Effectiveness, cardiac toxicity and lidocaine plasma concentrations were then determined.Results: No cardiac arrhythmias were observed, and lidocaine was effective in 76% of the treatments. In most of the treatments (13 out of 20) maximal lidocaine plasma concentrations were >9 mg/L. Plasma levels >9 mg/L have been related to cardiac toxicity when used as an anti-arrhythmic drug in adults. It was of interest that all preterm infants showed high lidocaine plasma levels. Secondly, we developed the optimal dosing regimen, which was defined as an infusion regimen at which maximal lidocaine plasma concentrations are <9 mg/L. Simulations with the developed pharmacokinetic model indicated a reduction in the infusion duration of lidocaine at 6 mg/kg per hour from 12 to 6 h. Thirdly, the new lidocaine dosing regimen was evaluated. Fifteen neonates (16 treatments) were studied. No cardiac arrhythmias were observed, and lidocaine was effective in 78% of the treatments. In most of the treatments (11 out of 16) maximal lidocaine plasma concentrations were <9 mg/L. Again preterm infants showed relatively high lidocaine plasma levels.Conclusion: A new lidocaine dosing schedule was developed. This new regimen should have a lower risk of cardiac arrhythmias and appears to be as effective in term infants. For preterm infants the optimal regimen needs to be determined. [ABSTRACT FROM AUTHOR]

Discusses the use of spontaneous reports of adverse events to estimate the risk for developing cardiac arrhythmias due to the systemic use of nonsedating antihistamine drugs in the Netherlands. Risk estimate before and after the regulatory action to recall the over-the-counter status of some of these drugs; Indication that nonsedating antihistamines might have an increased risk for inducing arrhythmias.

Background: The subcutaneous cardioverter-defibrillator (S-ICD) continues to be preferentially used in relatively young patients, with less advanced heart disease., Objective: We, therefore, studied the short and long-term efficacy and safety of the S-ICD in subgroups of patients, which are underreported at present., Methods: A total of 218 patients between November 2010 and February 2019 undergoing S-ICD with a follow up of at least 6 months implantation were included in a prospective registry. Mean follow up was 38 months., Results: The most common indication for S-ICD implantation was ischemic cardiomyopathy (n = 106, 49%). Complication rate needing invasive intervention was 9% (n = 21). Appropriate shock rate in patients with an S-ICD was 3.5%/year. A total of 30 inappropriate shocks (IAS) occurred in 19 patients (8.7%; 2.7%/year). The proportion of appropriate and inappropriate shock rates in patients with different cardiomyopathies shows remarkable variances. There were significant more IAS (3.6%/year vs. 1.7%/year, p = .048) in patients with non-ischemic cardiomyopathy versus patients with ischemic cardiomyopathy. Multivariate analysis identified, besides type of cardiomyopathy, atrial fibrillation (AF) as predictor for IAS., Conclusion: In this real-world prospective registry we analyzed S-ICD performance in the more traditional ICD patient. Patients with ischemic cardiomyopathy had significantly less inappropriate therapy compared to patients with non-ischemic cardiomyopathy and appear to be appropriate patients for this type of device., (© 2021 Wiley Periodicals LLC.)

Studies early afterdepolarizations (EAD) by researchers from Maastricht, Netherlands. Investigation on the role of EAD on the development of conduction block, prolonged repolarization-dependent reexcitation and tachyarrythmias in the human heart; Induction of EAD in the experimental laboratory; Efforts of the researchers to develop better criteria to differentiate between mechanisms of arrhythmias and to develop refined and reliable tecnniques to prove the existence of different mechanisms.

Aims: To estimate the incidence of direct oral anticoagulant drug (DOAC) use in patients with nonvalvular atrial fibrillation and to describe user and treatment characteristics in 8 European healthcare databases representing 6 European countries., Methods: Longitudinal drug utilization study from January 2008 to December 2015. A common protocol approach was applied. Annual period incidences and direct standardisation by age and sex were performed. Dose adjustment related to change in age and by renal function as well as concomitant use of potentially interacting drugs were assessed., Results: A total of 186 405 new DOAC users (age ≥18 years) were identified. Standardized incidences varied from 1.93-2.60 and 0.11-8.71 users/10 000 (2011-2015) for dabigatran and rivaroxaban, respectively, and from 0.01-8.12 users/10 000 (2012-2015) for apixaban. In 2015, the DOAC incidence ranged from 9 to 28/10 000 inhabitants in SIDIAP (Spain) and DNR (Denmark) respectively. There were differences in population coverage among the databases. Only 1 database includes the total reference population (DNR) while others are considered a population representative sample (CPRD, BIFAP, SIDIAP, EGB, Mondriaan). They also varied in the type of drug data source (administrative, clinical). Dose adjustment ranged from 4.6% in BIFAP (Spain) to 15.6% in EGB (France). Concomitant use of interacting drugs varied between 16.4% (SIDIAP) and 70.5% (EGB). Cardiovascular comorbidities ranged from 25.4% in Mondriaan (The Netherlands) to 82.9% in AOK Nordwest (Germany)., Conclusion: Overall, apixaban and rivaroxaban increased its use during the study period while dabigatran decreased. There was variability in patient characteristics such as comorbidities, potentially interacting drugs and dose adjustment. (EMA/2015/27/PH)., (© 2019 European Medicines Agency. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Introduction: Mechanisms of arrhythmogenicity in hypertrophic cardiomyopathy (HCM) are not well understood. Hypothesis: We hypothesized that HCM is characterized by specific electrophysiological (EP) substrate as compared to patients with the well-understood arrhythmogenic substrate (ischemic cardiomyopathy), as well as to individuals free from the arrhythmogenic substrate. Methods: We conducted a prospective case-control study. HCM patients (n=10; age 61±9 y; left ventricular ejection fraction (LVEF) 60±9%) were included if had either (1) documented history of sustained ventricular tachyarrhythmia (VT/VF) or resuscitated sudden cardiac arrest (SCA), or (2) LV wall thickness of > 30mm, or (3) extensive fibrosis on cardiac MRI (>15% of total myocardial volume), or (4) >7.5%/5-year risk of SCA. Three groups of controls included: (1) Healthy individuals (n=10; age 28±6 y; LVEF>70%), (2) Post-infarction (MI) patients with LV hypertrophy (LVH) and arrhythmogenic substrate as proven by the history of SCA or sustained VT/VF with appropriate ICD shock, (n=10; age 64±9 y; LVEF 31±15%), (3) Post-MI patients with LVH, presumably free from arrhythmogenic substrate (n=10; age 70±7y; LVEF 46±16%). All participants underwent 12-lead ECG, cardiac CT or MRI, and 128-electrodes body surface mapping (BioSemi ActiveTwo, Netherlands). Non-invasive epicardial activation maps were reconstructed using inverse solutions approach. Spatial ventricular gradient (SVG) magnitude and direction, vector magnitude QT integral (VMQTi), and spatial QRS-T angle were measured. Results: HCM patients had the widest QRS-T angle [130°±48° vs. 126°±50° (post-MI with VT/VF) vs. 108°±46° (post-MI no arrhythmia) vs. 60±23 (Healthy); P=0.003], and the largest VMQTi (166±81 vs. 84±34 mV*ms (post-MI with VT/VF) vs. 120±42 mV*ms (post-MI no arrhythmia) vs. 115±19 mV*ms (Healthy); P=0.008). SVG vector pointed higher up in HCM (SVG elevation 92°±33° vs. 80°±17° (post-MI with VT/VF) vs. 71°±21° (post-MI no arrhythmia) vs. 59°±9° (Healthy); P=0.011). Activation map in HCM was characterized by increased heterogeneity (Figure). Conclusions: HCM is characterized by increased global electrical heterogeneity, representing HCM-specific arrhythmogenic EP substrate. [ABSTRACT FROM AUTHOR]

Background: Although QRS duration >180 ms has prognostic value in adults with tetralogy of Fallot (TOF), its sensitivity to predict mortality is low. Fragmented QRS complexes, a simple measurement on ECG, are related to myocardial fibrosis and dysfunction in patients with TOF. Our objective was to determine whether QRS fragmentation predicts major outcomes in TOF.Methods: This multicentre study included adult patients with TOF from a prospective registry. Notches in the QRS complex in ≥2 contiguous leads on a 12-lead ECG, not related to bundle branch block, were defined as QRS fragmentation, which was classified as none, moderate (≤4 leads) or severe (≥5 leads). The primary and secondary outcomes were all-cause mortality and clinical ventricular arrhythmia, respectively.Results: A total of 794 adult patients with TOF (median age 27 years, 55% male; 52% no QRS fragmentation, 32% moderate, 16% severe) were included. During long-term (median 10.4 years) follow-up, 46 (6%) patients died and 35 (4%) patients had ventricular arrhythmias. Overall, 10-year survival was 98% in patients without fragmented QRS complexes, 93% in patients with moderate QRS fragmentation and 81% in patients with severe QRS fragmentation. In multivariable Cox hazards regression analysis, extent of QRS fragmentation (HR: 2.24/class, 95% CI 1.48 to 3.40, p<0.001) remained independently predictive for mortality, whereas QRS duration was not predictive (p=0.85). The extent of QRS fragmentation was also independently predictive for ventricular arrhythmia (HR: 2.00/class, 95% CI 1.26 to 3.16, p=0.003).Conclusions: The extent of QRS fragmentation is superior to QRS duration in predicting mortality in adult patients with TOF and may be used in risk stratification. [ABSTRACT FROM AUTHOR]

Background: It is unclear whether sports participation in adults with repaired congenital heart disease is safe and has benefits., Methods: Congenital heart disease (ConHD) patients who underwent corrective surgery for Atrial Septal Defect, Ventricular Septal Defect, Pulmonary Stenosis, Tetralogy of Fallot or Transposition of the Great Arteries in our center between 1968 and 1980 were included, and participated in our longitudinal follow-up study with serial evaluations in 2001 and 2011. At both time points patients filled in questionnaires on sports participation, subjective physical functioning and quality of life. Exercise testing, echocardiogram and 24-hour continuous ambulatory ECG-monitoring were performed in both 2001 and 2011. All clinical events (re-intervention, arrhythmia, heart failure) were prospectively recorded., Results: No relationship was found between practicing sports and the occurrence of sudden death, PVCs or SVTs. Patients with moderate/complex forms of ConHD practiced fewer hours of sports compared with the general Dutch normative population. Patients with both simple and moderate/complex ConHD who practiced sports showed a higher exercise capacity. More favorable subjective physical functioning was found for moderate/complex patients who practiced sports., Conclusions: Adults with repaired ConHD are less often involved in sports than the Dutch general population. The patients that were engaged in sports show a higher exercise capacity than those who did not. Sports participation in patients with ConHD was not associated with an increased incidence of adverse cardiac events., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Sudden unexplained death syndrome (SUDS) in young individuals often results from inherited cardiac disease. Accordingly, comprehensive examination in surviving first-degree relatives unmasks such disease in approximately 35% of the families. It is unknown whether individuals from diagnosis-negative families are at risk of developing manifest disease or cardiac events during follow-up., Objective: This study aimed to study the prognosis of first-degree relatives of young SUDS victims, in whom the initial cardiologic and genetic examination did not lead to a diagnosis., Methods: We retrieved vital status of surviving first-degree relatives from 83 diagnosis-negative families who presented to our cardiogenetics department between 1996 and 2009 because of SUDS in ≥1 relatives aged 1-50 years. Moreover, we contacted relatives who previously visited our center for detailed information., Results: We obtained detailed information (median follow-up 6.6 years; interquartile range 4.7-9.6 years) in 340 of 417 first-degree relatives (81.5%) from 77 of 83 families (92.8%). Vital status, available in 405 relatives (97.1%), showed that 20 relatives (4.9%) died during follow-up, including 1 natural death before the age of 50. This girl belonged to a family with multiple cases of idiopathic ventricular fibrillation and SUDS, including another successfully resuscitated sibling during follow-up. Two hundred thirty-four of 340 first-degree relatives (68.8%) underwent cardiologic examination. Of these, 76 (32.5%) were reevaluated. Inherited cardiac disease was diagnosed in 3 families (3.6%)., Conclusion: In first-degree relatives of young SUDS victims with no manifest abnormalities during the initial examination, the risk of developing manifest inherited cardiac disease or cardiac events during follow-up is low. This does not apply to families with obvious familial SUDS., (Copyright © 2014 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Discusses a case control study using data from the Dutch health care system that found that use of antipsychotic medication is associated with an increased risk of sudden cardiac death. Effects of antipsychotics on the QT interval that may result in cardiac arrhythmia; Lack of association between thioridazine and cardiac death; Median age of the study population.

Aims: To determine whether atrial-based pacing prevents atrial arrhythmias in adults with congenital heart disease (CHD) compared with ventricular pacing., Methods and Results: All adult CHD patients from four participating centres with a permanent pacemaker were identified. Patients with permanent atrial arrhythmias at pacemaker implantation and patients who received a pacemaker for treatment of drug-refractory atrial arrhythmias were excluded. The final study population consisted of 211 patients (52% male, 36% complex CHD) who received a first pacemaker for sick sinus dysfunction (n = 82) or atrioventricular block (n = 129) at a median age of 24 years [interquartile range (IQR), 12-34]. A history of atrial arrhythmias at implantation was present in 49 patients (23%). Atrial-based pacing was the initial pacing mode in 139 patients (66%) while the others (34%) received ventricular pacing. During a median follow-up of 13 years (IQR, 7-21), 90 patients (43%) developed an atrial arrhythmia. Multivariate analysis demonstrated no significant effect of atrial-based pacing on subsequent atrial arrhythmias [hazard ratio (HR), 1.53; 95% confidence interval (CI), 0.91-2.56; P = 0.1]. Independent predictors of atrial arrhythmia were history of atrial arrhythmias (HR, 5.55; 95% CI, 3.47-8.89; P< 0.0001), older age (≥18 years) at pacemaker implantation (HR, 2.29; 95% CI, 1.29-4.04; P = 0.005), and complex CHD (HR, 1.57; 95% CI, 1.01-2.45; P = 0.04)., Conclusion: In contrast to the general population, atrial-based pacing was not associated with a lower incidence of atrial arrhythmia in adults with CHD.